SMARCA4 biology in alveolar rhabdomyosarcoma.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
02
04
2021
accepted:
20
01
2022
revised:
21
12
2021
pubmed:
31
1
2022
medline:
20
4
2022
entrez:
30
1
2022
Statut:
ppublish
Résumé
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and phenocopies a muscle precursor that fails to undergo terminal differentiation. The alveolar subtype (ARMS) has the poorest prognosis and represents the greatest unmet medical need for RMS. Emerging evidence supports the role of epigenetic dysregulation in RMS. Here we show that SMARCA4/BRG1, an ATP-dependent chromatin remodeling enzyme of the SWI/SNF complex, is prominently expressed in primary tumors from ARMS patients and cell cultures. Our validation studies for a CRISPR screen of 400 epigenetic targets identified SMARCA4 as a unique factor for long-term (but not short-term) tumor cell survival in ARMS. A SMARCA4/SMARCA2 protein degrader (ACBI-1) demonstrated similar long-term tumor cell dependence in vitro and in vivo. These results credential SMARCA4 as a tumor cell dependency factor and a therapeutic target in ARMS.
Identifiants
pubmed: 35094009
doi: 10.1038/s41388-022-02205-0
pii: 10.1038/s41388-022-02205-0
pmc: PMC9985831
mid: NIHMS1787372
doi:
Substances chimiques
Nuclear Proteins
0
Transcription Factors
0
SMARCA4 protein, human
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1647-1656Subventions
Organisme : NCI NIH HHS
ID : P01 CA013106
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA045508
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA258720
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA245859
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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